Pediatric nephrology practice in Jordan.

The practice of pediatric nephrology in a developing country such as Jordan is governed by social, cultural, and economic issues. The prevalence of consanguinity contributes to the emergence of rare heredofamilial disorders and congenital anomalies of the kidneys and urinary tract. Epigenetic factors modify underlying genetic defect predisposing to symptomatic crystalluria. Future research should be directed at prevention.

Molecular analysis of the CTNS gene in Jordanian families with nephropathic cystinosis / Análisis molecular del gen CTNS en familias jordanas afectadas por cistinosis nefropática

Objetivo: La cistinosis nefropática es una enfermedad de almacenamiento lisosómico autosómica recesiva que se caracteriza por la acumulación del aminoácido cistina en varios tejidos del cuerpo. Ello se debe a una mutación en el gen CTNS, que codifica la proteína cistinosina. El objetivo de este estudio fue secuenciar los exones codificantes del gen CTNS en cinco familias jordanas afectadas por la cistinosis. Métodos: Los casos índice se presentaron inicialmente con síntomas del síndrome de Fanconi. Exámenes oftalmológicos revelaron la acumulación de cristales de cistina en la córnea a la edad de 2 años, lo que sugería la existencia de cistinosis. Todos los exones codificantes, las secuencias intrónicas flanqueantes y la región promotora del gen CTNS se amplificaron mediante reacción en cadena de la polimerasa y fueron objeto de secuenciación. Resultados: Ninguno de los casos índice de este estudio presentaba la deleción 57-kb europea en el gen CTNS. Se identificaron siete variantes en las secuencias codificante y promotora del gen CTNS en los casos índice de este estudio. Dos de estas variantes eran una mutación del gen CTNS previamente identificada en un genotipo heterocigótico de dos pacientes de descendencia europea. Las dos mutaciones eran c.829dupA en el exón 10 y c.890G>A en el exón 11. El caso índice de la familia número 2 era heterocigótico compuesto respecto a las dos mutaciones. Conclusión: El presente estudio es el primer estudio molecular sobre cistinosis nefropática infantil en Jordania. Logramos identificar con éxito las mutaciones en el gen CTNScausante en familias jordanas. Los resultados sirven de base para la detección precoz de esta enfermedad mediante herramientas moleculares en una población jordana marcadamente consanguínea (AU)

Objective: Nephropathic cystinosis is an autosomal recessive lysosomal storage disorder that is characterised by the accumulation of the amino acid cystine in several body tissues due to a mutation in the CTNS gene, which encodes the cystinosin protein. The aim of this study was to sequence the coding exons of the CTNS gene in five different Jordanian families and one family from Sudan with nephropathic cystinosis. Methods: Probands initially presented with Fanconi syndrome symptoms. An eye examination showed the accumulation of cystine crystals in the cornea by the age of 2 years, suggesting cystinosis. All of the coding exons and flanking intronic sequences and the promoter region of the CTNS gene were amplified using polymerase chain reaction and subjected to sequencing. Results: None of the probands in this study carried the European 57-kb deletion in the CTNS gene. Seven variants in the coding and promoter sequence of the CTNS gene were identified in the probands of this study. Two of these variants were a CTNS mutation that was previously identified in a heterozygous genotype in two different patients of European descendant. The two mutations were c.829dupA in exon 10 and c.890G>A in exon 11. The proband of family 2 was compound-heterozygous for the two mutations. Conclusion: This study is the first molecular study of infantile nephropathic cystinosis in Jordan. We successfully identified the causative CTNS mutations in Jordanian families. The results provide a basis for the early detection of the disease using molecular tools in a highly consanguineous Jordanian population (AU)

Molecular analysis of the CTNS gene in Jordanian families with nephropathic cystinosis.

OBJECTIVE: Nephropathic cystinosis is an autosomal recessive lysosomal storage disorder that is characterised by the accumulation of the amino acid cystine in several body tissues due to a mutation in the CTNS gene, which encodes the cystinosin protein. The aim of this study was to sequence the coding exons of the CTNS gene in five different Jordanian families and one family from Sudan with nephropathic cystinosis. METHODS: Probands initially presented with Fanconi syndrome symptoms. An eye examination showed the accumulation of cystine crystals in the cornea by the age of 2 years, suggesting cystinosis. All of the coding exons and flanking intronic sequences and the promoter region of the CTNS gene were amplified using polymerase chain reaction and subjected to sequencing. RESULTS: None of the probands in this study carried the European 57-kb deletion in the CTNS gene. Seven variants in the coding and promoter sequence of the CTNS gene were identified in the probands of this study. Two of these variants were a CTNS mutation that was previously identified in a heterozygous genotype in two different patients of European descendant. The two mutations were c.829dupA in exon 10 and c.890G>A in exon 11. The proband of family 2 was compound-heterozygous for the two mutations. CONCLUSION: This study is the first molecular study of infantile nephropathic cystinosis in Jordan. We successfully identified the causative CTNS mutations in Jordanian families. The results provide a basis for the early detection of the disease using molecular tools in a highly consanguineous Jordanian population.

Hypercalcemia, hypercalciuria and nephrocalcinosis in a breast-fed term newborn: a rare presentation.

Although hypercalcemia and hypercalciuria are known to occur in breast-fed pre-term infants, to the best of our knowledge, it has never been reported in a term baby previously. We report a term male baby who was followed-up during pregnancy for having bright kidneys, but a follow-up renal ultrasound (US) after birth had revealed normal scan. Laboratory investigations revealed normal serum calcium (Ca), phosphorous (PO4) and alkaline phosphatase (ALP). The baby was being fed by breast milk. Follow-up US two months later showed early nephrocalcinosis along with hypercalcemia and hypercalciuria; by the age of three months, nephrocalcinosis was more extensive and the serum Ca level was more than 12 mg/L with hypercalciuria. Parathyroid hormone (PTH), phosphorous (PO4), ALP and thyroid function tests were all normal. Antenatal history revealed a hypothyroid mother who was maintained on L-thyroxin, calcium and vitamin D supplement during pregnancy. Her blood tests showed normal serum Ca, low PO4 and elevated PTH. The baby was diagnosed to have hypercalciuria and hypercalcemia secondary to maternal hypophosphatemia (maternal vitamin D deficiency). Breast feeding was stopped and the baby was started on formula, whereby he showed remarkable improvement both for his blood chemistry as well as his hypercalciuria.

Pediatric renal transplantation: Jordan's experience.

To evaluate our experience with pediatric renal transplantation at King Hussein Medical Center, the medical records of 71 pediatric patients who underwent a renal transplantation procedure between the years 2004 and 2010 or started follow-up at our center within one week of transplantation done elsewhere were reviewed. Over the seven-year period, 71 children under the age of 14 years who received their first renal transplant were studied. About 56% (40) were males. The mean age was 9.44 ± 2.86 years. Dysplastic kidney was the most common cause of end-stage renal failure in our group, followed by glomerulonephritis. Mothers were the donors in 39.4% of the cases, followed by fathers. Twenty-three patients (32.4%) were transplanted preemptively. The overall one-year graft survival was 96%, three-year survival was 95%, and the five-year survival was 88%. Prednisone, tacrolimus, and mycophenolate mofetil formed the main-stay of immunosuppressive agents. We have developed a successful live donor program for renal transplantation in children at King Hussein Medical Center in Amman. Although our experience is still short, the graft survival is similar to that achieved in the developed world, especially with preemptive transplant.

Pediatric renal transplantation in the jordanian population: the clinical outcome measures during long-term follow-up period.

INTRODUCTION: Recently, many international studies have suggested that pediatric patients from diverse ethnic origins confront unique challenges for transplantation. Data concerning the efficacy and safety of transplantation for various pediatric renal transplant populations remains limited and are often confounded by immunosuppressive protocols. In one study, we aimed to evaluate the short- and long-term outcomes of renal transplants in Jordanian children in comparison with groups of different nationalities. METHODS: We retrospectively retrieved data for 34 Jordanian children who received kidney transplants from living donors between January 2003 and January 2009. Subsequently, we continued to follow-up with these selected patients at scheduled clinic visits to prospectively collect long-term data for a period of approximately 22 months±15 months. RESULTS: The patients included in this study ranged between 4 years and 19 years of age. The male/female ratio was 0.79. Glumerulonephritis (35.3%) was the most common cause of end-stage renal disease in the sample of this study; 23.5% had received a preemptive transplant. All patients also received triple immunosuppressive therapy, consisting of tacrolimus (TAC), prednisolone, and mycophenolate mofetil (n=26) or azathioprine (n=8). Furthermore, the rate of acute rejection episodes was lower in the sample of this study than the average rate of many previous studies. The patients' survival rate at 1 year, 2 years and 3 years posttransplant was nearly 100%. The corresponding graft survivals were 97.1%, 94.12% and 91.2% respectively. Beyond three years, one female patient died postgraft loss. This graft loss was mainly attributed to recurrent glomerulonephritis. Strikingly, the prevalence of posttransplant diabetes (PTD) and hypertension was higher than reported international figures. Other adverse events, such as infections, were manageable. CONCLUSION: The average result of pediatric renal transplantation in Jordan is more successful than the average results of this procedure in many developed countries, especially in terms of early graft function, acute rejection episodes as well as long-term patient and graft survivals. However, additional studies are needed to better characterize pharmacokinetic of TAC and to fully understand those factors that lead to an increased probability of developing conditions like PTD and hypertension.

The effect of rectourogenital fistula in high imperforate anus.

To determine the incidence of rectourogenital fistulae and the possible role of fistulae on the mechanism of defecation in patients with high imperforate anus, we retrospectively studied 42 children, 38 males and four females, all with high imperforate anus presenting in the period from 1982 to 1995. All children underwent radiological evaluation, to determine the level of the rectal pouch 18-24 hours after birth and to study the bony spine. A preliminary colostomy was performed in all patients after the diagnosis shortly after birth. Ultrasonography was performed in all the cases to assess the kidneys and ureters. All patients but one was operated on via a posterior sagittal anorectoplasty. Bowel control was assessed clinically regarding the presence of voluntary bowel movement, fecal soiling, incontinence and constipation. Eighteen (42.8%) patients were found to have recto-urogenital fistulae; 15 rectourethral, two rectovaginal and one rectovesical. Outcomes were known for 36 out of 42 patients; 15(41.6 %) had voluntary bowel movements, nine (25 %) had soiling, six (16.6%) had constipation and six (16.6 %) had incontinence. In conclusion, the presence of rectourogenital fistula in patients with high imperforate anus is another new prognostic factor for anorectal function which needs further clarification.

Familial focal segmental glomerulosclerosis and retinitis pigmentosa: a new association.

The association of retinitis pigmentosa with renal disease is rare and occurs mainly in two conditions: medullary cystic disease and Bardet-Biedl syndrome; here we describe a case of retinitis pigmentosa with familial focal segmental glomerulosclerosis, which to the best of our knowledge has never been reported previously.

Ectopia vasa deferentia inguinal hernia, vesicourteric reflux, imperforate anus, and recto-vesical fistula: a case report.

Urologic congenital anomalies are frequently associated with anorectal abnormalities. Vas deferens anomalies in the general population are estimated to be less than 0.05%. Many of the abnormalities can be explained by events in early fetal life. Urosepsis and epididymitis are the usual presenting signs and symptoms in such patients. We describe an infant who was discovered after birth to have an association of high imperforate anus with recto-vesical fistula, right inguinal hernia, left vesicoureteral reflux, and bilateral dilated vasa deferentia ectopically terminating in the posterior urethra, which caused recurrent epididymo-orchitis.

Pediatric end-stage renal disease: single center analysis.

Data describing end stage renal disease in Jordan is very limited, due to the absence of internal center as well as national registry systems. In this retrospective analysis, we define the etiology, prevalence, incidence as well as other demographic features of pediatric end stage renal disease and renal replacement therapy at King Hussein Medical Center. All children who entered the chronic dialysis program in our center from January 2001 to December 2005 were included in the study. Children who were transplanted pre-emptively were also included. A total number of 42 patients were included. The mean age at time of dialysis initiation was 11.10+/-2.25 years; 19 (45.2%) were males. The prevalence of ESRD in Jordan children was calculated to be 14.5 patients per million. Hemodialysis (HD) was the primary modality of therapy in 40 (95.2%) patients. The most common cause of ESRD in our children was acquired glomerulopathy in 13 (31%) patients, followed by oxalosis in seven (16.7%), and neurogenic bladder in six (14.3 %). Thirteen patients were transplanted; the one and three year graft survival rates were 87.5% and 72.5%, respectively. We conclude that there are some peculiar features for pediatric ESRD in Jordan including the high incidence of oxalosis and neurogenic bladder. A national registry for children with ESRD should be established as this may have serious implications on the choice of renal replacement therapy.

Primary nocturnal enuresis among school children in jordan.

We attempted in this study, to estimate the prevalence of primary nocturnal enuresis (PNE) in children of Jordan, and to examine factors associated with PNE. We sent questionnaires to 950 parents of children aged 6-8 years, randomly selected from three primary schools in Jordan. The questionnaire was designed to evaluate the prevalence and factors associated with PNE. The response rate was 71.6%. The overall prevalence of PNE was 23.8%. This prevalence declined with age from 48.9% at 6 years to 21.1% at 7 years and 8.4% at 8 years. Our findsings indicate that the prevalence of PNE in Jordan is higher than that reported from other Asian or European countries, while the associated factors are similar.

Cyclosporine-a therapy in steroid dependent nephrotic syndrome: experience in amman, jordan.

The use of Cyclosporin-A (CsA) has been well described and is currently recommended for use in patients with steroid dependent nephrotic syndrome (SDNS), especially when they start having steroid side effects. Over a three-year period, a total of 10 patients diagnosed as having SNDS at the King Hussein Medical Center, Amman, Jordan were retrospectively studied. Their mean age was 9.53 +/- 4.9 years. All patients included in the study failed to maintain long-term remission following cyclophosphamide therapy and had all manifested at least one steroid side effect prior to the introduction of CsA. Kidney biopsy was performed on all patients and all had normal renal functions prior to the introduction of CsA. After inducing remission with conventional steroid therapy, CsA was given in a dose of 4-6 mg/Kg/day orally in two divided doses and adjusted to maintain a mean blood trough level between 100 and 150 ng/ml. Total duration of therapy ranged between six and 24 months with a mean of 17 +/- 7.7. Steroid therapy was stopped in all patients within two months of starting CsA. Four patients relapsed after 4-6 months of stopping steroids. However, remission was re-induced when low dose alternate day prednisolone therapy was added. Two patients relapsed four months after stopping CsA, which was given for 24 months. Our study suggests that CsA is effective in maintaining long-term remission and decreasing steroid requirements in patients with SDNS.